1993 Fiscal Year Annual Research Report

球状3D構造をもつペプチド性超分子構造体の分子機能設計

Research Project

Project/Area Number	05671872
Research Institution	The University of Tokushima
Principal Investigator	堀均徳島大学, 工学部, 助教授 (90119008)
Keywords	ペプチド / Arg-Arg配列 / ペプチド性超分子構造体 / 分枝状超分子構造体 / 分子認識 / 分子機能設計 / 大腸吸収 / ドラッグデリバリーシステム
Research Abstract	本研究は,簡単なアミノ酸を合成原料として球状3D構造をもつペプチド性超分子構造体の分子機能設計および,その抗体産生や分子認識分子や大腸吸収ドラッグデリバリーシステム用ベクターなどの生物工学的応用を目的とする.これは,構造的特徴から比較的半減期が長いが最終的には分解されることが予想され「身体にやさしい薬」の開発が可能であると考え本研究を企画した. 1.構造体の表面極性を考慮したペプチド性超分子構造体の分子機能設計:L-Lysの両アミノ基を橋頭堡としL-Lysをn回結合させ末端が2^<n+1>個のアミノ基をもつ分枝状超分子構造体のコアに認識配列をもつペプチドを結合し,目的とする極性表面をもつペプチド性超分子構造体を独自の新規分子設計法により構築した. 2.大腸吸収ドラッグデリバリーシステム用ベクターとしてのペプチド性超分子構造体の分子機能設計:C末端が遊離したArg-Arg配列などをシグナルペプチドとした球状3D構造をもつペプチド性超分子構造体を分子設計した.これを現有の反転大腸を用い薬物吸収実験装置を用い,ペプチドのサイズ,吸収率,非分解性などを検討し,最適な薬物ベクターとして(H-RLLL)_8K_4K_2K AAALLLRR-OHの構造体を分子機能設計し創製した. 3.ペプチド性超分子構造体の生物工学的応用:以上新規分枝状超分子構造体の構築によるタンパク質の分子機能設計により,DNAを情報源とする1次配列からの従来の生物工学的方法から脱却できることを確認し総括した.

Research Products
(10 results)

All Other

All Publications (10 results)

[Publications] Hamada,N., 他7人: "The Enhancement of Tumor Growth Suppression and The Inhibition of Lung Metastasis Induced by Radiosensitizer" J.Jpn Soc.Ther.Radiol.Oncol.5. 68 (1993)
[Publications] Li,Z., 他8人: "Peptide α-Keto Ester,α-Keto Amide,and α-Keto Acid Inhibitors of Calpains and Other Cysteine Porteases" J.Med.Chem.36. 3472-3480 (1993)
[Publications] Nakagawa,Y.,H.Hori,I.Yamamoto,and H.Terada: "Characteristic Bleaching Profiles of Cyanine Dyes Depending on Active Oxygen Species in the Controlled Fenton Reaction" Biol.Pharm.Bull.16. 1061-1064 (1993)
[Publications] Pan,N.,H.Hori: "Acteoside:An Inhibitor of Mitochondrial Lipid Peroxidation" Lipid Peroxide Res.17. 55 (1993)
[Publications] Hori,H. 他5人: "KIH-201:A New Enhancer of Chemiluminescence in the Luminol-hydrogen peroxide-peroxidase System Characterized by a High-performace Luminometer" Anal.letters. 27 in press. (1994)
[Publications] Pan,N.and H.Hori.: "The Interaction of Acteoside with Mitochondrial Lipid Peroxidation as an Ischemia/Reperfusion Injury Model." Adv.Exp.Med.Biol.in press. (1993)
[Publications] Tada,T. 他6人: "In vivo Radiosensitizing Effect of Nitroimidazole Derivative KIN-814" Int.J.Radiation Oncology Biol.Phys.(in press). (1994)
[Publications] Powers,J.C. 他6人: "Proteases-Structures,Mechanism and Inhibitors,Proteases,Protease Inhibitors and Protese-Derived Peptides" Ed.J.C.Cheronis and J.E.Repine.Birkhaeuser Verlag, 330 (1993)
[Publications] Hori,H.,H.Nagasawa,and H.Terada.: "Effects of Free Radicals from Hypoxic Cell Radiosensitizers,Hypoxic Cell Cytotoxins,and Bioreductive Anticancer Drugs on the Biological Environment.Oxidants in the Environment" Ed.J.O.Nriagu and M.S.Simmons,John Wiley & Sons, 425-443 (1994)
[Publications] Terada.H,S.Goto,H.Hori,and Z.Taira: "Structural Requirements of Leukotriene Antagonists" Ed.by T.Fujita QSAR-New Approaches and Examples.ELsevier Science Publishers, in press (1994)

1993 Fiscal Year Annual Research Report

球状3D構造をもつペプチド性超分子構造体の分子機能設計

Principal Investigator

堀 均 徳島大学, 工学部, 助教授 (90119008)

Research Products

[Publications] Hamada,N., 他7人: "The Enhancement of Tumor Growth Suppression and The Inhibition of Lung Metastasis Induced by Radiosensitizer" J.Jpn Soc.Ther.Radiol.Oncol.5. 68 (1993)

[Publications] Li,Z., 他8人: "Peptide α-Keto Ester,α-Keto Amide,and α-Keto Acid Inhibitors of Calpains and Other Cysteine Porteases" J.Med.Chem.36. 3472-3480 (1993)

[Publications] Nakagawa,Y.,H.Hori,I.Yamamoto,and H.Terada: "Characteristic Bleaching Profiles of Cyanine Dyes Depending on Active Oxygen Species in the Controlled Fenton Reaction" Biol.Pharm.Bull.16. 1061-1064 (1993)

[Publications] Pan,N.,H.Hori: "Acteoside:An Inhibitor of Mitochondrial Lipid Peroxidation" Lipid Peroxide Res.17. 55 (1993)

[Publications] Hori,H. 他5人: "KIH-201:A New Enhancer of Chemiluminescence in the Luminol-hydrogen peroxide-peroxidase System Characterized by a High-performace Luminometer" Anal.letters. 27 in press. (1994)

[Publications] Pan,N.and H.Hori.: "The Interaction of Acteoside with Mitochondrial Lipid Peroxidation as an Ischemia/Reperfusion Injury Model." Adv.Exp.Med.Biol.in press. (1993)

[Publications] Tada,T. 他6人: "In vivo Radiosensitizing Effect of Nitroimidazole Derivative KIN-814" Int.J.Radiation Oncology Biol.Phys.(in press). (1994)

[Publications] Powers,J.C. 他6人: "Proteases-Structures,Mechanism and Inhibitors,Proteases,Protease Inhibitors and Protese-Derived Peptides" Ed.J.C.Cheronis and J.E.Repine.Birkhaeuser Verlag, 330 (1993)

[Publications] Hori,H.,H.Nagasawa,and H.Terada.: "Effects of Free Radicals from Hypoxic Cell Radiosensitizers,Hypoxic Cell Cytotoxins,and Bioreductive Anticancer Drugs on the Biological Environment.Oxidants in the Environment" Ed.J.O.Nriagu and M.S.Simmons,John Wiley & Sons, 425-443 (1994)

[Publications] Terada.H,S.Goto,H.Hori,and Z.Taira: "Structural Requirements of Leukotriene Antagonists" Ed.by T.Fujita QSAR-New Approaches and Examples.ELsevier Science Publishers, in press (1994)

堀均徳島大学, 工学部, 助教授 (90119008)